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Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. 1997

B E van den Borne, and B A Dijkmans, and H H de Rooij, and S le Cessie, and C L Verweij
Department of Rheumatology, Leiden University Hospital, The Netherlands.

OBJECTIVE The efficacy of both chloroquine and hydroxychloroquine in rheumatoid arthritis (RA) has been proved in controlled clinical trials. Despite similar chemical characteristics, it is believed the clinical efficacy of chloroquine is superior to that of hydroxychloroquine in patients with RA. Excessive production of proinflammatory cytokines was shown to contribute to the pathogenesis of RA. From different studies testing either chloroquine or hydroxychloroquine, it could be concluded that both drugs differentially inhibit cytokine production. METHODS We compared the effects of both chloroquine and hydroxychloroquine on stimulated peripheral blood mononuclear cells (PBMC) with respect to cytokine production. Therefore, PBMC were tested for tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interferon-gamma (IFN-gamma) by specific ELISA, after stimulation with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) in the presence or absence of different concentrations of chloroquine or hydroxychloroquine. RESULTS We observed that chloroquine and hydroxychloroquine equally inhibit PHA induced TNF-alpha and IFN-gamma production, and LPS induced TNF-alpha and IL-6 production, while PHA induced IL-6 production was not affected. CONCLUSIONS Chloroquine and hydroxychloroquine display similar effects on PHA and LPS induced cytokine production by PBMC under identical in vitro conditions. These findings may help in understanding the mechanism of action of these drugs on RA.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008297 Male Males
D010835 Phytohemagglutinins Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture. Kidney Bean Lectin,Kidney Bean Lectins,Lectins, Kidney Bean,Phaseolus vulgaris Lectin,Phaseolus vulgaris Lectins,Phytohemagglutinin,Hemagglutinins, Plant,Lectin, Kidney Bean,Lectin, Phaseolus vulgaris,Lectins, Phaseolus vulgaris,Plant Hemagglutinins
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002738 Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006886 Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970) Hydroxychlorochin,Oxychlorochin,Oxychloroquine,Hydroxychloroquine Sulfate,Hydroxychloroquine Sulfate (1:1) Salt,Plaquenil
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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